Abstract 20465: The Anti-fibrotic and Anti-inflammatory Potentials of Purified Human Muscle-derived Perivascular Cells for the Treatment of Myocardial Infarction
Perivascular cells, pericytes in particular, isolated from multiple human tissues have been shown to harbor stem cells endowed with mesodermal developmental potentials. Transplantation of multipotent muscle-derived pericytes repair and regenerate damaged/dystrophic skeletal and heart muscles in vivo as well as improve cardiac function post-infarction. Previously we demonstrated that pericytes support formation of vascular structures and promote angiogenesis after acute myocardial infarction. In the current study, we further investigated the hypothesis that transplantation of human muscle-derived pericytes into the ischemic myocardium results in anti-fibrotic and anti-inflammatory effects upon improvement of cardiac function. Purified CD34-/45-/56-/146+ pericytes were injected into acutely infarcted myocardium of immunodeficient mice (3.0×105 cells per heart). To evaluate the anti-fibrotic effect of purified pericytes in vivo, we estimated myocardial fibrosis 2 weeks post-infarction by Masson's trichrome staining. Histological analysis revealed a 38% reduction of the scar area in pericyte-injected hearts when compared to saline-injected controls. We theorized a role of donor cell-derived matrix metalloproteinases (MMPs) in such a reduction of fibrosis specifically under the hypoxic microenvironment. To illustrate MMP levels produced by donor pericytes, cells were cultured in vitro under 2.5% oxygen for 24 hours. Real-time quantitative PCR analysis revealed a sustained high expression of MMP-2 but not MMP-9 by pericytes under hypoxia. We next examined the anti-inflammatory effect of pericytes by histologically quantifying the presence of host CD68+ monocytes/macrophages in the infarct area 2 weeks post-injection. The infiltration of CD68+ cells was significantly reduced in pericyte-injected hearts, suggesting the reduction of inflammation contributed to the improvement of cardiac remodeling. When co-cultured with pericytes in vitro, the proliferation of stimulated peripheral blood mononuclear cells was inhibited, providing further evidence of the immunomodulation. Overall, our data suggests a role of pericyte-mediated anti-scarring and anti-inflammatory effects in the post-infarction cardiac repair.
- © 2010 by American Heart Association, Inc.